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  • Authors: Harry L. T. Mobley1, Michael S. Donnenberg2, and Erin C. Hagan3
  • Editor: Michael S. Donnenberg4
    Affiliations: 1: Departments of Medicine and Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD 21201; 2: Departments of Medicine and Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD 21201; 3: Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI 48109-0620; 4: University of Maryland, School of Medicine, Baltimore, MD
  • Received 01 May 2009 Accepted 07 August 2009 Published 21 December 2009
  • Address correspondence to Harry L. T. Mobley [email protected].
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  • Abstract:

    The urinary tract is among the most common sites of bacterial infection, and is by far the most common species infecting this site. Individuals at high risk for symptomatic urinary tract infection (UTI) include neonates, preschool girls, sexually active women, and elderly women and men. that cause the majority of UTIs are thought to represent only a subset of the strains that colonize the colon. strains that cause UTIs are termed uropathogenic (UPEC). In general, UPEC strains differ from commensal strains in that the former possess extragenetic material, often on pathogenicity-associated islands (PAIs), which code for gene products that may contribute to bacterial pathogenesis. Some of these genes allow UPEC to express determinants that are proposed to play roles in disease. These factors include hemolysins, secreted proteins, specific lipopolysaccharide and capsule types, iron acquisition systems, and fimbrial adhesions. The current dogma of bacterial pathogenesis identifies adherence, colonization, avoidance of host defenses, and damage to host tissues as events vital for achieving bacterial virulence. These considerations, along with analysis of the CFT073, UTI89, and 536 genomes and efforts to identify novel virulence genes should advance the field significantly and allow for the development of a comprehensive model of pathogenesis for uropathogenic .Further study of the adaptive immune response to UTI will be especially critical to refine our understanding and treatment of recurrent infections and to develop vaccines.

  • Citation: Mobley H, Donnenberg M, Hagan E. 2009. Uropathogenic , EcoSal Plus 2009; doi:10.1128/ecosalplus.

Key Concept Ranking

Type 1 Fimbriae
Bacterial Pathogenesis
gamma delta T Cell
Type I Secretion System
Urinary Tract Infections


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The urinary tract is among the most common sites of bacterial infection, and is by far the most common species infecting this site. Individuals at high risk for symptomatic urinary tract infection (UTI) include neonates, preschool girls, sexually active women, and elderly women and men. that cause the majority of UTIs are thought to represent only a subset of the strains that colonize the colon. strains that cause UTIs are termed uropathogenic (UPEC). In general, UPEC strains differ from commensal strains in that the former possess extragenetic material, often on pathogenicity-associated islands (PAIs), which code for gene products that may contribute to bacterial pathogenesis. Some of these genes allow UPEC to express determinants that are proposed to play roles in disease. These factors include hemolysins, secreted proteins, specific lipopolysaccharide and capsule types, iron acquisition systems, and fimbrial adhesions. The current dogma of bacterial pathogenesis identifies adherence, colonization, avoidance of host defenses, and damage to host tissues as events vital for achieving bacterial virulence. These considerations, along with analysis of the CFT073, UTI89, and 536 genomes and efforts to identify novel virulence genes should advance the field significantly and allow for the development of a comprehensive model of pathogenesis for uropathogenic .Further study of the adaptive immune response to UTI will be especially critical to refine our understanding and treatment of recurrent infections and to develop vaccines.

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Image of Figure 1
Figure 1

Genome maps of pyelonephritis strains 536 and CFT073 and cystitis strain UTI89, indicating the relative locations of PAIs and genomic islands (all islands shown are >20 kb). Colors indicate islands homologous between strains, while gray represents strain-specific PAIs. An island was considered conserved between strains if the majority of PAI-associated genes were present and syntenic at the same chromosomal location; often small insertions and deletions are present. tRNA genes associated with each island (if applicable) are shown in the center and virulence factors encoded in each PAI are noted (virulence genes for homologous PAIs are shown only once). In addition to these large PAIs, numerous phage elements and small insertions are found in each genome and are not shown. Note: GI-CFT073- and PAI-CFT073- are annotated as a single island, PAI VI (), in 536 and UTI89 and the 22-kb PAI VII () is present, but unnamed in CFT073. PAIs were annotated according to previous studies ( 46 , 47 , 49 , 66 , 76 ) and BASE genome alignments. Brackets denote previous CFT073 PAI nomenclature.

Citation: Mobley H, Donnenberg M, Hagan E. 2009. Uropathogenic , EcoSal Plus 2009; doi:10.1128/ecosalplus.
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Image of Figure 2
Figure 2

Arrows represent ORFs and are shaded according to gene product, as indicated. Inset shows the 314-bp invertible element (shown with promoter [P] in the ON orientation), responsible for phase variation of the operon. White, inverted repeats (IR) that flank the promoter region. Yellow, binding sites of FimB and FimE recombinases.

Citation: Mobley H, Donnenberg M, Hagan E. 2009. Uropathogenic , EcoSal Plus 2009; doi:10.1128/ecosalplus.
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Figure 3

FimB, FimE, IpuA, and IpbA (FimX) recombinases are shown in yellow with annotation below indicating the activity of each enzyme on invertible element orientation. Regulatory proteins IHF, Lrp, and H-NS mediate many of these effects by binding to sequences within the invertible element and either positively (arrow) or negatively (blocked arrow) affecting FimB and FimE function. Signals influencing IpuA and IpbA function are unknown. GlcNAc, -acetylglucosamine.

Citation: Mobley H, Donnenberg M, Hagan E. 2009. Uropathogenic , EcoSal Plus 2009; doi:10.1128/ecosalplus.
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Figure 4

Infection proceeds in an ascending manner, beginning with periurethral colonization and progressing from bladder to kidney colonization. Attachment of UPEC to superficial umbrella cells and kidney epithelium is mediated by type 1 (inset, shown in blue) and P fimbriae (inset, shown in green), respectively. Bladder tissue damage is a result of UPEC binding, invasion, and possibly toxin secretion (i.e., CNF-1, hemolysin). Upregulation of flagella facilitate progression to the kidney, where P fimbriae binding, LPS shedding, and toxin secretion may induce inflammation, recruit neutrophils (PMNs), and cause renal damage. Bacteremia can occur if bacteria cross the two cell layers separating the kidney from the bloodstream.

Citation: Mobley H, Donnenberg M, Hagan E. 2009. Uropathogenic , EcoSal Plus 2009; doi:10.1128/ecosalplus.
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Table 1

Prevalence of virulence determinants among UTI and fecal isolates

Citation: Mobley H, Donnenberg M, Hagan E. 2009. Uropathogenic , EcoSal Plus 2009; doi:10.1128/ecosalplus.
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Table 2

Prototypic strains used in UTI research

Citation: Mobley H, Donnenberg M, Hagan E. 2009. Uropathogenic , EcoSal Plus 2009; doi:10.1128/ecosalplus.
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Table 3

Ferric iron acquisition systems of UPEC

Citation: Mobley H, Donnenberg M, Hagan E. 2009. Uropathogenic , EcoSal Plus 2009; doi:10.1128/ecosalplus.
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Table 4

Virulence determinants of UPEC

Citation: Mobley H, Donnenberg M, Hagan E. 2009. Uropathogenic , EcoSal Plus 2009; doi:10.1128/ecosalplus.

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